CHAPTER 42 The Thyroid Gland lipolysis, ketogenesis, and proteolysis of the labile protein pool. The overall metabolic effect of thyroid hormone has been aptly described as accelerating the physiological response to starvation. In addition, thyroid hormone stimulates synthesis of bile acids from cholesterol and promotes biliary secretion. The net effect is a decrease in the body pool and plasma levels of total and low-density lipoprotein cholesterol. Metabolic clearance of adrenal and gonadal steroid hormones, some B vitamins, and certain administered drugs is also increased by thyroid hormone.
Thyroid hormones stimulate thermogenesis by affecting both adenosine triphosphate (ATP) utilization and the efficiency of ATP synthesis. ATP utilization is enhanced by upregulation of several energy-dependent processes, including Na+,K+-ATPase and SERCA, particularly in skeletal muscle, where calcium cycling between the cytoplasm and sarcoplasmic reticulum uses ATP and generates heat. Recently it has been demonstrated that brown fat in humans, once thought to be important only in neonates, appears to play a role in facultative thermogenesis in adults. Imaging studies have demonstrated the presence of brown fat in the mediastinum, particularly in lean individuals, and metabolic activity in brown fat is enhanced by exposure to cold. Brown fat expresses uncoupling protein-1 (UCP1), also called thermogenin, which causes the proton gradient across the inner mitochondrial membrane to be dissipated as heat, which is then disseminated to the rest of the body by the circulation. UCP1 is regulated by thyroid hormone, and brown fat expresses D2, providing intracellular conversion of T4 to T3. Brown fat thermogenesis involves a synergistic interaction between thyroid hormones and the sympathetic nervous system. Catecholamines promote lipolysis and upregulate expression of D2. T3 in turn upregulates adrenergic receptors and enhances catecholamine responsiveness. Hyperthyroidism is accompanied by heat intolerance, whereas hypothyroidism is accompanied by cold intolerance.
Thyroid hormone stimulates O2 utilization and enhances O2 delivery. Appropriately, T3 increases the resting respiratory rate, minute ventilation, and the ventilatory response to hypercapnia and hypoxia. These actions maintain a normal arterial PO2 when O2 utilization is increased and a normal PCO2 when CO2 production is increased. Additionally the hematocrit increases slightly to enhance O2-carrying capacity. This increase results from stimulation of erythropoietin production by the kidney.
Normal function of skeletal muscles also requires optimal amounts of thyroid hormone. This requirement may be related to regulation of energy production and storage. Glycolysis and glycogenolysis are increased, whereas glycogen and creatine phosphate are reduced by thyroid hormone excess. The inability of muscle to take up and phosphorylate creatine leads to its increased urinary excretion.
Effects on the Autonomic Nervous System and Catecholamine Action
As already mentioned, there is important synergism between catecholamines and thyroid hormones. Thyroid hormones are synergistic with catecholamines in increasing the metabolic rate, heat production, heart rate, motor activity, and excitation of the CNS. T3 may enhance sympathetic nervous system activity by increasing the number of β-adrenergic receptors in heart muscle and the generation of intracellular second messengers such as cyclic adenosine monophosphate (cAMP).